Abstract 4563: Measuring immunotherapy responses <i>ex vivo</i> using novel 3D culture platform: E-slice
Authors: Thomas D. Gallup, Jose A. Maldonado, Corina Margain, Min P. Kim, David F. Gallup, Kyuson Yun
Journal: Cancer Research (2023)

Abstract Immunotherapies have provided dramatic and life-saving results in some patients; however, their effectiveness varies greatly in different tumors, even among patients with the same clinical diagnosis. Clearly, a better system to evaluate the personalized response to immunotherapies will greatly benefit the patients and reduce the cost of care. In addition, due to their theoretical and demonstrated benefits in providing durable responses, new immunotherapies are avidly sought after by most major pharmaceutical companies, numerous biotech companies, and academic laboratories. However, preclinical evaluation of new immunotherapy efficacy is challenging and inaccurate using most experimental model systems.E-slice is a faithful model of an individual cancer patient’s tumor. It is a proprietary 3D tissue slice culture platform, and E-slices are generated by making thin sections of intact, fresh tumor tissues from patients. As such, immune components and the TME in E-slices are native to each patient’s tumor. E-slice overcomes many of the limitations of other experimental systems for multiple reasons. The E-slice platform: 1) uses chemically defined, serum-free medium; 2) measures viability changes upon treatment longitudinally, from the same tissue, which allows both absolute and relative responses for as short as 4 days or as long as over 4 weeks ex vivo; 3) can be generated from any solid tumor tested thus far (breast, lung, colorectal, pancreas, brain, head 7 neck, and others) from patient tumors directly or from PDX and genetically engineered mouse models; 4) retains the native TME and tissue architecture because E-slices are never dissociated or otherwise reconstituted; 5) is compatible with biopsies as well as surgical samples; 6) has been shown to accurately predict individual patient treatment responses to chemotherapies and targeted therapies in 4-12 days, paving the way for evidence-based personalized treatment selections in a clinically actionable time frame.Specifically for immunotherapy response measurements, key differentiators of the E-slice platform from other ex vivo systems for immunotherapy responses are: 1) E-slice is generated from fresh patient tumor tissues with tumor-trained and resident immune cells and not artificially introduced PBMCs used in most other systems; 2) serum-free, chemically defined medium and does not artificially activate or suppress the immune system; 3) E-slice has been validated by single-cell RNA-sequencing to maintain immune cells in their native state up to 8 days ex vivo; 4) E-slices can be used to detect secreted protein and metabolic biomarkers in the conditioned media pre- and post-treatment; 5) E-slice can measure immunotherapy responses ex vivo in 8 days. In summary, we present a novel ex vivo 3D human tumor tissue drug sensitivity platform that can enhance immunotherapy development pipelines and clinical deployment. Citation Format: Thomas D. Gallup, Jose A. Maldonado, Corina Margain, Min P. Kim, David F. Gallup, Kyuson Yun. Measuring immunotherapy responses ex vivo using novel 3D culture platform: E-slice. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4563.